Transfemoral transcaval liver access and devices

ABSTRACT

Shaped liver biopsy sheaths and methods for transfemoral transcaval liver access are disclosed.

CROSS-REFERENCE TO RELATED APPLICATION

This application is a continuation of application of U.S. applicationSer. No. 15/533,384, filed Jun. 6, 2017, which is a national phase ofInternational Application No. PCT/US2016/013576, filed Jan. 15, 2016,which claims the benefit of U.S. Provisional Patent Application No.62/103,821, filed on Jan. 15, 2015, the content of which is hereinincorporated by reference into the subject application.

BACKGROUND OF THE INVENTION

Throughout this application various publications are referred to inparentheses. Full citations for these references may be found at the endof the specification. The disclosures of these publications are herebyincorporated by reference in their entirety into the subject applicationto more fully describe the art to which the subject invention pertains.

Liver biopsy is the gold standard for the evaluation of acute andchronic liver disease. Percutaneous liver biopsy (PLB) remains thepreferred approach in most situations; however, transjugular liverbiopsy (TJLB) (1) can be performed where there are contraindications toa percutaneous approach, such as coagulopathy, thrombocytopenia orascites where PLB may be prone to bleeding (2-4). TJLB is consideredsafer in these situations since any bleed will most likely beintravascular.

However, TJLBs can be difficult, and there are potential complications.TJLB requires hepatic vein cannulation through which the biopsy specimenis obtained. Difficulties include negotiating a stiffened cannula intoacutely angled hepatic veins; maintaining a stiff cannula in the hepaticvein during movement caused by the patient's respiration while avoidinginjury of the hepatic vein/liver junction, and the need for twooperators—one to hold the cannula and one to remove the biopsy specimenfrom the needle.

Biopsies performed directly through the inferior vena cava (IVC) from ajugular approach have also been described in instances when a hepaticvein could not be cannulated (5). Difficulties with this approach caninclude difficult jugular access and the need to traverse and exit theright atrium (RA) into the IVC.

The present invention provides procedures and devices for a transfemoraltranscaval (TFTC) approach for liver biopsies that is expected to besafer, easier and more reliable than a transjugular approach.

SUMMARY OF THE INVENTION

The present invention provides methods of obtaining a tissue sample fromthe liver of a patient, the methods comprising inserting a hollowsheath, such as a stiffened sheath with an angled tip, through a femoralvein into a portion of the inferior vena cava (IVC) adjacent to theliver, wherein the sheath's tip is in the intrahepatic IVC and whereinthe sheath has a shape that brings the tip of the sheath adjacent to thewall of the IVC at an angle that is optimal to allow penetration of thewall of the IVC by a biopsy needle, and inserting a biopsy needlethrough the sheath and through the wall of the IVC into the liver toobtain a tissue sample from the liver.

The invention also provides kits for obtaining a tissue sample from theliver of a patient, the kits comprising an outer flexible vascularsheath having a length that extends from a femoral vein to theintrahepatic portion of the inferior vena cava (IVC) of the patient; ahollow sheath, such as a stiffened angled sheath, capable of passingthrough the outer flexible sheath, wherein the sheath is preshaped withone or more bends and/or is capable of being shaped in vivo to providean angle between the tip of the sheath and the longitudinal axis of thesheath between >30 degrees to 90 degrees, and wherein the hollow sheathis longer than the outer flexible vascular sheath; and a flexible biopsyneedle capable of passing through the hollow sheath to penetrate thewall of the IVC and pass into the liver to obtain a tissue sample fromthe liver, wherein the flexible biopsy needle is longer than the hollowsheath.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1. Schematic of venous anatomy and an example of an outer flexiblevascular sheath 110. The femoral veins are to the right of the venousdiagram. IVC—inferior vena cava, RA—right atrium. Drawing not to scale.

FIG. 2. Illustration of an example of a schematic of an outer flexiblevascular sheath 210 inserted through the femoral vein into the IVC tothe level of the liver and of a preshaped rigid hollow sheath 220 thatcan be inserted through the outer flexible vascular sheath. Drawing notto scale.

FIG. 3. Illustration of an example of a shapeable semirigid hollowsheath 320 (and dilator 330) that can be inserted over a guidewire 340into the IVC. The assembly is shown in the upper view of the figure. Theguidewire 340 and dilator 330 can be removed from the hollow sheath 320(middle view) and the hollow sheath can be shaped in vivo into anoptimal shape for a transcaval liver biopsy (lower view). Drawing not toscale.

FIG. 4. Illustration of an example of an inner hollow sheath 420 thathas been advanced through an outer flexible vascular sheath 410 so thata tip 425 of the inner hollow sheath 420 is positioned at a desiredangle relative to a wall 490 of the IVC. The inner hollow sheath 420 canbe a preshaped rigid hollow sheath or a shapeable semirigid hollowsheath having a tip 425 that can be shaped in vivo. A flexible biopsyneedle 580 (illustrated in FIG. 5) can be advanced through the innerhollow sheath 420 to penetrate the wall 490 of the IVC and obtain atissue sample from the liver. Drawing not to scale.

FIG. 5. Examples of a flexible biopsy needle 580. Left—example of aflexible biopsy needle 580 demonstrating range of flexibility. A window585 for collecting the biopsy sample is open. Right—example of aflexible biopsy needle 580 with the core biopsy window closed.

FIG. 6. Illustration of example selective catheters 605 a and 605 b.

DETAILED DESCRIPTION OF THE INVENTION

The present invention provides a method of obtaining a tissue samplefrom a liver of a patient, via a transfemoral transcaval route, themethod comprising:

inserting a hollow sheath through a femoral vein into a portion of theinferior vena cava (IVC) adjacent to the liver, wherein the sheath's tipis in the intrahepatic IVC and wherein the sheath has a shape thatbrings the tip of the sheath adjacent to the wall of the IVC at an anglethat is optimal to allow penetration of the wall of the IVC by a biopsyneedle, and

inserting a biopsy needle through the sheath and through the wall of theIVC into the liver to obtain a tissue sample from the liver.

The sheath can be preshaped with one or more bends before the sheath isinserted into the patient. Alternatively, or in addition, the sheath canbe shaped in vivo after the sheath is inserted into the IVC. The sheathmay have, for example, one bend 222 or 322 (FIGS. 2 or 3) near the tipand a secondary bend 322 or 323 (FIGS. 2 or 3) in the longitudinal axisof the sheath farther from the tip.

The sheath can be inserted through an outer vascular sheath that hasbeen inserted through the femoral vein into the IVC.

The sheath and/or outer vascular sheath can be inserted in the IVC withthe aid of a guidewire.

The sheath has a main longitudinal body that can contain one or morebends (e.g., bends 222, 223, 322, and/or 323 illustrated in FIG. 2 or 3)to angle the tip of the sheath so that it is optimal to allowpenetration of the wall of the IVC by a biopsy needle. The angle of thetip is indicated in reference to the longitudinal axis of the main bodyof the sheath (i.e., the main part of the sheath that is not bent). Theangle between the tip of the sheath and the longitudinal axis of thesheath is preferably between >30 degrees to 90 degrees or 35-90 degreesor 40-90 degrees. In one embodiment, the angle between the tip of thesheath and the longitudinal axis of the sheath is between 40-80 degrees.In one embodiment, the angle between the tip of the sheath and thelongitudinal axis of the sheath is between 50-70 degrees.

Preferred sheaths include those that are malleable to allow eintroduction of secondary bends along the main body of the sheath.

The invention also provides a kit for obtaining a tissue sample from theliver of a patient, the kit comprising:

-   -   an outer flexible vascular sheath having a length that extends        from a femoral vein to an intrahepatic portion of the inferior        vena cava (IVC) of the patient;    -   a hollow sheath capable of passing through the outer flexible        sheath, wherein the sheath is preshaped with one or more bends        and/or is capable of being shaped in vivo to provide an angle        between the tip of the sheath and the longitudinal axis of the        sheath between >30 degrees to 90 degrees, and wherein the hollow        sheath is longer than the outer flexible vascular sheath; and    -   a flexible biopsy needle capable of passing through the hollow        sheath to penetrate the wall of the IVC and pass into the liver        to obtain a tissue sample from the liver, wherein the flexible        biopsy needle is longer than the hollow sheath.

The kit can also include a guidewire to add insertion and placement ofthe outer flexible vascular sheath and/or hollow sheath in the IVC;and/or a dilator.

In different embodiments, the angle between the tip of the sheath andthe longitudinal axis of the sheath is between 35-90 degrees, 40-90degrees, 40-80 degrees or 50-70 degrees.

The kits disclosed herein can be used for obtaining a tissue sample fromthe liver of a patient.

The components of the present invention can be made from standardmaterials used in vascular surgery and biopsies. For example, the outervascular sheath can be a 10-F sheath of 38.5 cm, such as provided, forexample, by Cook, Inc., Bloomington, Ind. The guidewire, if used, canbe, for example, a 0.035-inch guide wire.

The preshaped sheath can be, for example, a 7-F stiffened cannula. Suchcannulas can be provided by Argon Medical Devices, Inc., Athens, Tex.The preshaped sheath can have a precurved protective metallic insert orstiffener 227 (FIG. 2). The preshaped sheath needs to be preshaped withone or more bends to provide an angle of incidence of the tip of thesheath with respect to the wall of the IVC that is optimal to allowpenetration of the wall of the IVC by a biopsy needle. Existingpreshaped devices on the market are not meant to be reshaped, due toconcerns about damaging the device. Accordingly, no preshaped devicecurrently exists on the market that provides a tip angle suitable for atransfemoral transcaval liver biopsy as disclosed herein. Alternatively,or in addition to, a preshaped sheath, the sheath can be shaped in vivousing, for example, a mechanical handle 330 (FIG. 3) at the external endof the sheath. Catheters with ends that can be adjusted to change shapehave been described, for example, in U.S. Pat. No. 7,402,151 B2(BioCardia, Inc., South San Francisco, Calif.), the contents of whichare herein incorporated by reference. Whereas preshaped sheaths willtypically be advanced into the IVC through a pre-positioned outervascular sheath, flexible sheaths that can be shaped in vivo may notneed to be advanced into the IVC through a pre-positioned outer vascularsheath due to the flexibility of the sheath. The length of the sheathneeds to be sufficient to reach from the femoral vein to theintrahepatic IVC of the patient and can be, for example, about 70 cmlong.

The flexible biopsy needle can be, for example, a 19-gauge biopsy needlewith a 20-mm throw, such as provided, for example, by Argon MedicalDevices, Inc., Athens, Tex. Biopsy devices are described, for example,in U.S. Pat. Nos. 6,419,641 B1, 7,078,694 B2 and 7,841,990 B2 (PromexTechnologies, LLC, Franklin, Ind.), the contents of which areincorporated herein. The biopsy needle needs to be longer than thesheath so that the needle can penetrate the wall of the IVC and enterthe liver.

Placement of the sheaths and biopsy needle can be monitored by real-timeimaging of the patient.

Advantages of the transfemoral, transcaval approach disclosed hereininclude:

-   -   no need for jugular access and its inherent complications,    -   no need to cross the right atrium and its inherent complications        (arrhythmias, tamponade, etc.),    -   no need to advance a rigid cannula into a hepatic vein,    -   multiple biopsies can be obtained without the need to hold the        cannula in place,    -   a single operator can perform the entire procedure—perform        biopsy and remove the specimen from needle, and    -   pressures (RA, IVC, HV and/or Wedge PV) can be easily obtained        from the femoral route.

This invention will be better understood from the Experimental Details,which follow. However, one skilled in the art will readily appreciatethat the specifics discussed are merely illustrative of the invention asdescribed more fully in the claims that follow thereafter.

EXPERIMENTAL DETAILS Example I—Overview of Obtaining Hepatic TissueThrough the Inferior Vena Cava Through a Femoral Venous Approach

The invention involves inserting a sheath through a femoral vein intothe inferior vena cava (IVC) to the level of the liver of a patient. Theadvancement and positioning the sheath can be monitored by real-timeimaging of the patient. Examples of sheaths that can be used areillustrated in FIGS. 1-4. A biopsy needle is then inserted through thesheath to penetrate the wall of the IVC and obtain a tissue sample fromthe liver. The sheath is positioned so that the angle of incidence ofthe tip of the sheath with respect to the wall of the IVC is optimal toallow penetration of the wall of the IVC by the biopsy needle.

FIGS. 1 and 2 illustrate an example of a vascular sheath that isinserted through a femoral vein to the intrahepatic IVC. The sheath canbe positioned in the vasculature using a guidewire. FIG. 4 illustratesan example of an inner sheath positioned though an outer vascular sheathso that the tip of the inner sheath is at a desired angle with respectto the wall of the IVC. The inner sheath can be preshaped prior to beinginserted through the outer vascular sheath (e.g., FIG. 2, Item2—preshaped rigid sheath). Alternatively, the tip of the sheath can beshaped after the sheath is placed into the intrahepatic IVC (e.g., FIG.3), in which case an outer vascular sheath may not be required.

Example II—Obtaining Hepatic Tissue Through the Inferior Vena CavaThrough a Femoral Venous Approach. This Example is Summarized fromCynamon, J., et al. (9). See Also (10)

Materials and Methods

The institutional review board approved this retrospective study.Sixty-six cases of transfemoral transcaval (TFTC) liver biopsies (65.2%male; mean age, 53.2±15.0 years) were reviewed. One patient underwentthree TFTC biopsies; each was counted individually.

Abnormal coagulation parameters were defined by institutional laboratorythresholds. All patients with an international normalized ratio ≥1.8 orplatelet count <50,000/μL were transfused with fresh frozen plasma orplatelets, respectively, immediately before the procedure, during theprocedure, or both. Intravenous fentanyl and midazolam were administeredfor sedation at the operator's discretion. Patient oxygen saturation,hemodynamics, and electrocardiographic parameters were monitored duringthe case. After biopsy, patients were observed and vital signs weremonitored for at least 4 hours. Procedure-related complications wereclassified according to Society of Interventional Radiology (SIR)guidelines (6).

Right common femoral venous access was obtained using the Seldingertechnique, and a 38.5-cm-long 10-F sheath (Flexor® Check-Flo® II; Cook,Inc., Bloomington, Ind.) was placed over a 0.035-inch guidewire into theinferior vena cava (IVC). The sheath dilator was then exchanged for aselective catheter, such as a 5-F Cobra selective catheter 605 a (Cook,Inc.) or a 6-F Judkins Left 4 selective catheter 605 b (Cook, Inc.)illustrated in FIG. 6. The catheter was used to select a hepatic vein tomeasure hepatic venous pressure.

Next, the catheter was exchanged for a physician-modified (with slightincrease in curvature) precurved 7-F stiffened cannula (Argon MedicalDevices, Plano, Tex.), which was advanced through the long sheath overthe guide wire and positioned in the intrahepatic IVC. This cannula wasdirected toward the lateral caval wall within the intrahepatic portionof the IVC at a level deemed favorable based on imaging.

Next, a 19-gauge biopsy needle (Flexcore, Argon Medical Devices) with a20-mm throw was advanced through the caval wall, and the biopsy needlewas fired under fluoroscopic observation. The stiffened cannula wasrepositioned slightly more inferiorly, and a second biopsy specimen wasobtained in a similar fashion. Tissue samples were examined by theoperator, and if deemed inadequate, additional samples were obtained. Avenogram was then obtained through the sheath to document absence ofcaval injury before removal.

Results and Discussion

Hepatic tissue samples were obtained in 64 out of 66 cases (97%).Sufficient tissue for histopathologic diagnosis was obtained in 63 cases(95.5%). Complications after biopsy occurred in only two patients (3%),which were successfully treated. One of the two was a decrease inhemoglobin and the second was a self-limiting fever. No bleedingcomplications were observed.

One advantage of the TFTC approach is that the procedure does notrequire traversing the right atrium, which occasionally may be difficultor lead to arrhythmias (2,7,8). This method also avoids the need toadvance and maintain a stiff cannula in a hepatic vein, and obviatesnegotiating problematic hepatic venous anatomy. Performing the biopsydirectly from the IVC also does not necessitate a lateral view todistinguish between the right and middle hepatic veins when the correctcatheter position is in question (2,7), as is required for the TJLBprocedure. Additionally, the biopsy needle is deployed within the liverdirectly through the intrahepatic IVC away from central vessels so thatarterial and capsular injuries may be avoided. Finally, positioning andmaintaining the physician-modified cannula against the lateral cavalwall during and between biopsies does not require more than oneoperator. The overall technical and histopathologic success rates inthis study, which were 97.0% and 95.5%, respectively, are similarcompared to prior large case series of TJLBs (2,3,7,8). TFTC liverbiopsies are safe and have advantages over TJLB.

REFERENCES

-   1. Rosch J, Lakin P C, Antonovic R, Dotter C T. Transjugular    approach to liver biopsy and transhepatic cholangiography. N Engl J    Med 1973; 289: 227-231.-   2. Mammen T, Keshava, S N, Eapen C E, et al. Transjugular liver    biopsy: a retrospective analysis of 601 cases. J Vasc Intery Radiol    2008; 19: 351-358.-   3. Smith T P, Presson T L, Heneghan M A, Ryan J M. Transjugular    biopsy of the liver in pediatric and adult patients using an    18-gauge automated core biopsy needle: a retrospective review of 410    consecutive procedures. AJR Am J Roentgenol 2003; 180:167-172.-   4. Bruzzi J F, O'Connell M J, Thakore H, O'Keane C, Crowe J, Murray    J G. Transjugular liver biopsy: assessment of safety and efficacy of    the Quick-Core biopsy needle. Abdom Imaging 2002; 27:711-715.-   5. Moses V, Keshava S N, Mammen S, Ahmed M, Eapen C E,    Ramakrishna B. Trans-caval trans jugular liver biopsy—a technical    modification of trans jugular liver biopsy. Br J Radiol 2014;    87:20140327.-   6. Sacks D, McClenny T E, Cardella J F, Lewis C A. Society of    Interventional Radiology clinical practice guidelines. J Vasc Intery    Radiol 2003; 14:S199-5202.-   7. Gamble P, Colapinto R F, Stronell R D, Colman J C, Blendis L.    Transjugular liver biopsy: a review of 461 biopsies. Radiology 1985;    157:589-593.-   8. Dohan A, Guerrache Y, Dautry R, et al. Major complications due to    transjugular liver biopsy: incidence, management and outcome. Diagn    Intery Imaging 2015; 96:571-577.-   9. Cynamon J, Shabrang C, Golowa Y, Daftari A, Herman O, Jagust M.    Transfemoral Transcaval Core-Needle Liver Biopsy: An Alternative to    Transjugular Liver Biopsy. J Vasc. Interv. Radiol., Epub Dec. 23,    2015, 6 pages.-   10. Daftari A, Golowa Y, Jagust M, Herman O, Cynamon J. Feasibility    of transcaval needle core biopsies from a femoral vein approach. J    Vasc. Interv. Radiol., February 2015: 26(2): S84.

What is claimed is:
 1. A system for obtaining a tissue sample from aliver of a patient via a transfemoral-transcaval approach, the systemcomprising: a hollow sheath having a main longitudinal body and a tipconfigured to be angled away from a longitudinal axis defined by atleast an unbent portion of the main longitudinal body, wherein: thehollow sheath has a first length, the hollow sheath is configured forinsertion into an inferior vena cava (IVC) of the patient via a femoralvein of the patient, the hollow sheath has a fixed shape prior toinsertion into the patient, the fixed shape includes a first bend at afirst location on the main longitudinal body and a second bend at asecond location on the main longitudinal body farther from the tip thanthe first location, the first bend includes a first radius of curvatureand the second bend includes a second radius of curvature, the firstradius of curvature is less than the second radius of curvature, and thetip is generally positioned along the first bend such that the firstbend directs an opening at the tip toward a wall of the IVC when thehollow sheath is positioned in a portion of the IVC; and a flexiblebiopsy needle having a second length greater than the first length,wherein the flexible biopsy needle is configured to pass through thehollow sheath, penetrate a wall of the IVC, and obtain a tissue samplefrom the liver of the patient.
 2. The system of claim 1, wherein thehollow sheath is a stiffened or rigid sheath.
 3. The system of claim 1,wherein that the first bend and the second bend angle the tip between 30degrees and 90 degrees away from the longitudinal axis.
 4. The system ofclaim 1, wherein that the first bend and the second bend angle the tipbetween 40 degrees and 80 degrees away from the longitudinal axis. 5.The system of claim 1, wherein that the first bend and the second bendangle the tip between 50 degrees and 70 degrees away from thelongitudinal axis.
 6. The system of claim 1, wherein the hollow sheathis a semirigid sheath such that the hollow sheath and/or the tip aremalleable and shapeable in vivo.
 7. The system of claim 6, furthercomprising a mechanical handle at an external end of the hollow sheath,wherein the hollow sheath is shapeable via the mechanical handle.
 8. Thesystem of claim 6, wherein the hollow sheath is configured for insertioninto the IVC via the femoral vein without use of an outer flexiblevascular sheath.
 9. The system of claim 1, further comprising an outerflexible vascular sheath having a third length that extends at leastfrom the femoral vein to an intrahepatic portion of the IVC, wherein thethird length is less than the first and second lengths, and wherein thehollow sheath is configured to pass through the outer flexible vascularsheath.
 10. The system of claim 9, wherein the outer vascular sheath isa 10-F sheath.
 11. The system of claim 9, wherein the third length is38.5 cm.
 12. The system of claim 1, wherein the hollow sheath is a 7-Fstiffened cannula.
 13. The system of claim 1, wherein the hollow sheathfurther comprises a pre-curved protective metallic insert or stiffener.14. The system of claim 1, wherein the first length is about 70 cm. 15.The system of claim 1, wherein the biopsy needle is a 19-gauge biopsyneedle with a 20-mm throw.
 16. The system of claim 9, furthercomprising: a guidewire for insertion and placement of the outerflexible vascular sheath and/or the hollow sheath in the IVC; and/or adilator.
 17. The system of claim 16, further comprising the guidewire,wherein the guidewire is a 0.035 inch guide wire.
 18. The system ofclaim 1, further comprising a selective catheter, wherein the selectivecatheter is a 5-F or 6-F selective catheter.
 19. The system of claim 1,wherein the first bend is oriented in a first direction and the secondbend is oriented in the first direction.
 20. The system of claim 1,wherein the first bend is oriented in a first direction and the secondbend is oriented in a second direction different from the firstdirection.